U.S. Pat. No. 3,897,434 to Katner assigned to Eli Lilly and Company discloses various pyrazolo[1,5-c]-quinazolin-5(6H)-ones as being useful as anti-inflammatory agents, immunosuppressants or complement inhibitors. Katner indicates that some of the pyrazolo[1,5-c]quinazolin-5(6H)-ones of the structure ##STR2## wherein R.sup.1 is hydrogen or C.sub.1 -C.sub.3 -alkoxycarbonyl; R.sup.2 is C.sub.1 -C.sub.3 alkoxycarbonyl, acetyl, benzoyl or monosubstituted benzoyl in which the substituent is fluoro, chloro, bromo, C.sub.1 -C.sub.3 alkyl, or C.sub.1 -C.sub.3 alkoxy; and R.sup.3 is hydrogen, methyl, benzyl, or monosubstituted benzyl in which the substituent is fluoro, chloro or bromo; with the limitation that when R.sup.1 is hydrogen and R.sup.2 is C.sub.1 -C.sub.3 alkoxycarbonyl, R.sup.3 cannot be methyl, have the ability to suppress immune mechanisms in a host mammal as measured by the compound's activity as an anti-allergic agent.
"Immunosuppressant activity" is the property of a compound to inhibit the immune response of an animal to a specific antigen. Indeed, the procedure outlined in the Katner patent for testing of immunosuppressant activity involves the intraperitoneal injection of antigen (sheep red blood cells) into a group of mice that are subsequently treated for a period of time. The animals are bled on the seventh day after injection with antigen and the antibody titer in control and test animals are compared.
"Anti-allergic activity" is normally demonstrated by the passive cutaneous anaphylaxis reaction in rats. The skin of rats is first sensitized by the intradermal injection of reaginic (allergic) antibody. Twenty-four hours later, the animals receive a challenge injection of antigen together with Evan's blue dye given intravenously. The antigen, thus injected directly into the circulation, encounters the antibody in the skin and an "allergic reaction" occurs which is identified by the formation of intracutaneous edema. The edema is marked by the presence of the Evan's blue dye in the circulation. Test compounds are evaluated by their ability to prevent or diminish the amount of edema found as a result of inhibiting some phase of the allergic reaction.
Thus, the allergic reaction does not involve antibody formation as is observed for immunosuppressive activity. Likewise, immunosuppressive activity does not involve the formation of the allergic reaction. They are two distinct activities. Thus, anti-allergic activity is not a measure of a compound's activity as an immunosuppressant and vice versa. Furthermore, the fact that a compound has immunosuppressant activity does not make it predictable that it will have anti-allergy activity, and vice versa. However, it has been unexpectedly discovered that the pyrazolo[1,5-c]-quinazolin-5(6H)-ones described herein have anti-allergenic activity and are useful in the treatment of asthma.